Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity WE have previously reported that cutting the nigrostriatal dopamine-carrying axons unexpectedly results in a transient increase in the rate of tyrosine hydroxylation in the rat forebrain (Carlsson, Kehr & others, 1972). It was suggested that striatal tyrosine hydroxylase activity is controlled via dopamine receptors at the synaptic cleft : when the impulse flow is interrupted by axotomy, the concentration of dopamine in the synaptic cleft decreases, and the ensuing reduction of dopamine receptor activity gives rise to a feedback activation of tyrosine hydroxylase, located in the striatal dopaminecarrying nerve terminals. The experiments now reported were made to test the above hypothesis. We argued that stimulation and blockade of dopamine receptors should result in inhibition and activation, respectively, of striatal tyrosine hydroxylase activity. Male Sprague-Dawley rats, 210-340 g, were used. Axotomy of the nigrostriatal dopamine fibres was performed under ether anaesthesia on the left side by means of a transverse cerebral hemisection, as previously described (BCdard, Carlsson&Lindqvist, 1972). At the same time (or in some experiments after 1 h) the aromatic amino-acid decarboxylase was inhibited by an intraperitoneal injection of NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg). The animals
Journal of Pharmacy and Pharmacology: An International Journal of Pharmaceutical Science – Wiley
Published: Sep 1, 1972
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